Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance in Parkinson's Disease (PD)

A Phase II, Eight Week, Multi-Center, Open Label Trial of Xyrem(R) (Sodium Oxybate) for Excessive Daytime Sleepiness and Nocturnal Sleep Disturbance in Patients With Mild to Moderate Parkinson's Disease

This clinical trial is designed to evaluate the safety and potential efficacy of Xyrem for the treatment of excessive daytime sleepiness (EDS) and nocturnal sleep disturbance in patients with mild to moderate Parkinson's Disease (PD).

Inclusion required an Epworth Sleepiness Scale (ESS) score greater than 10 and any subjective nocturnal sleep concern, usually insomnia. An acclimation and screening polysomnogram was performed to exclude subjects with sleepdisordered breathing. The following evening, subjects underwent another polysomnogram, followed by an evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) while practically defined off ("off") PD medications, ESS (primary efficacy point), Pittsburgh Sleep Quality Inventory, and Fatigue Severity Scale. Subjects then started sodium oxybate therapy, which was titrated from 3 to 9 g per night in split doses (at bedtime and 4 hours later) across 6 weeks, and returned for subjective sleep assessments. They then returned at 12 weeks after initiating therapy for a third polysomnogram, an offmedication UPDRS evaluation, and subjective sleep assessments. Data are expressed as mean (SD).

Inclusion Criteria:

• Male or female with a diagnosis of idiopathic PD.
• Age between 30 and 75, inclusive. -Hoehn & Yahr Stage 1.5 - 4.0 in the practically defined medication "OFF". -
• History > 2 months of excessive daytime sleepiness confirmed at baseline/screening by an Epworth Sleepiness Scale score of > 10.
• History > 2 months of nocturnal sleep disturbances consisting of insomnia, fragmented sleep and/or non-restorative sleep.
• Folstein Mini-Mental State Exam score of > 24.
• Birth control for sexually active women of childbearing potential (e.g. abstinence, hormonal contraception, barrier method, intrauterine device).
• Evidence of a personally signed and dated informed consent form document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, and other study procedures.
• Stable dose of medications, defined as no change in dose or regimen of medications for at least 3 months prior to Screen Visit.

Exclusion Criteria:

• Known idiopathic sleep pathology: sleep apnea and narcolepsy.
• Serious co-morbid disease --Atypical parkinsonism (e.g., Parkinson "plus" syndrome, secondary Parkinson's syndrome). --Significant neurological symptoms not accounted for by PD. --Significant psychiatric symptoms or dementia.
• Sexually active women of childbearing potential without adequate form of birth control.
• Pregnancy or lactation.
• Mini-mental status examination of < 25.
• Participation in another clinical trial of another investigational agent or device within the previous 60 days.
• Current abuse of alcohol or drugs.
• Active or prior malignancy other than cutaneous basal cell carcinoma or in situ carcinoma of the uterine cervix.
• Known hypersensitivity to sodium oxybate or other constituents of the product.
• Any medical conditions that are contraindications to the use of sodium oxybate or significant hepatic impairment.
• Patients being treated with sedative hypnotic agents or other central nervous system (CNS) depressants.
• Subjects taking warfarin.
• Patients with succinic semialdehyde dehydrogenase deficiency.
• Subjects who, in the opinion of the investigator, are not able to comply with the requirements of the study.
• Any other condition that, in the investigator's opinion, would cause a significant hazard to the subject.